Chen Yu-Shan, Wang Jeng-Tzung, Chang Yu-Fong, Liu Bu-Yuan, Wang Yi-Ping, Sun Andy, Chiang Chun-Pin
Graduate Institutes of Oral Biology, National Taiwan University, Taipei, Taiwan.
J Oral Pathol Med. 2004 Apr;33(4):209-17. doi: 10.1111/j.0904-2512.2004.00118.x.
Hepatocyte growth factor (HGF) is a pleotropic growth factor that regulates cell proliferation, migration, survival, tumor angiogenesis, and tumor cell invasion and metastasis. Its diverse biological effects are mediated through its interaction with its receptor, c-met protein.
In this study, we examined the expression of HGF and c-met protein in 93 specimens of oral squamous cell carcinoma (OSCC), 10 specimens of oral epithelial dysplasia (OED), 14 specimens of oral epithelial hyperkeratosis (OEH), and 16 specimens of normal oral mucosa (NOM) by immunohistochemistry. The HGF and c-met labeling indices (LIs) in OSCC, OED, OEH, and NOM groups were calculated and compared between groups. The correlation between the expression of HGF or c-met in OSCCs and clinicopathological parameters, or survival of OSCC patients was analyzed statistically to investigate the possible influence of HGF or c-met on the progression and prognosis of OSCCs in Taiwan.
Positive HGF or c-met staining was mainly cytoplasmic. The mean HGF LI increased significantly from NOM (3.1 +/- 5.1%) through OEH (32.5 +/- 19.8%) and OED (52.0 +/- 19.3%) to OSCC (71.9 +/- 28.6%; P = 0.000). The mean c-met LI also increased significantly from NOM (25.8 +/- 30.8%) and OEH (34.4 +/- 19.3%) through OED (53.0 +/- 20.0%) to OSCC (73.0 +/- 29.4%; P = 0.000). Statistical analysis showed that the c-met LI in either the tumor center or invasion front was significantly associated with T status, N status, and clinical staging of OSCC. However, only the HGF LI in the tumor invasion front was significantly correlated with N status and clinical staging of OSCC.
Our results suggest that the expression of HGF and c-met protein is an early event in oral carcinogenesis in Taiwan. The HGF LI in the tumor invasion front and the c-met LI in either the tumor center or invasion front can predict the progression of OSCCs in Taiwan.
肝细胞生长因子（HGF）是一种多效生长因子，可调节细胞增殖、迁移、存活、肿瘤血管生成以及肿瘤细胞的侵袭和转移。其多种生物学效应是通过与受体c-met蛋白相互作用介导的。
在本研究中，我们采用免疫组织化学方法检测了93例口腔鳞状细胞癌（OSCC）标本、10例口腔上皮发育异常（OED）标本、14例口腔上皮过度角化（OEH）标本和16例正常口腔黏膜（NOM）标本中HGF和c-met蛋白的表达。计算OSCC、OED、OEH和NOM组中HGF和c-met的标记指数（LIs），并进行组间比较。对OSCC中HGF或c-met的表达与临床病理参数或OSCC患者生存率之间的相关性进行统计学分析，以研究HGF或c-met对台湾地区OSCC进展和预后的可能影响。
HGF或c-met阳性染色主要位于细胞质。HGF的平均LI从NOM（3.1±5.1%）经OEH（32.5±19.8%）和OED（52.0±19.3%）至OSCC（71.9±28.6%）显著增加（P = 0.000）。c-met的平均LI也从NOM（25.8±30.8%）和OEH（34.4±19.3%）经OED（53.0±20.0%）至OSCC（73.0±29.4%）显著增加（P = 0.000）。统计学分析表明，肿瘤中心或侵袭前沿的c-met LI与OSCC的T分期、N分期及临床分期显著相关。然而，仅肿瘤侵袭前沿的HGF LI与OSCC的N分期及临床分期显著相关。
我们的结果表明，HGF和c-met蛋白的表达是台湾地区口腔癌发生的早期事件。肿瘤侵袭前沿的HGF LI以及肿瘤中心或侵袭前沿的c-met LI可预测台湾地区OSCC的进展。
